scholarly journals The interplay between host genetics and the gut microbiome reveals common and distinct microbiome features for human complex diseases

2019 ◽  
Author(s):  
Fengzhe Xu ◽  
Yuanqing Fu ◽  
Ting-yu Sun ◽  
Zengliang Jiang ◽  
Zelei Miao ◽  
...  
Keyword(s):  
Renal Function ◽  
Gut Microbiome ◽  
Genome Wide Association Study ◽  
Causal Effect ◽  
Complex Diseases ◽  
Disease Etiology ◽  
Host Genetics ◽  
Genome Wide ◽  
Host Genetic ◽  
Human Complex

AbstractThere is increasing interest about the interplay between host genetics and gut microbiome on human complex diseases, with prior evidence mainly derived from animal models. In addition, the shared and distinct microbiome features among human complex diseases remain largely unclear. We performed a microbiome genome-wide association study to identify host genetic variants associated with gut microbiome in a Chinese population with 1475 participants. We then conducted bi-directional Mendelian randomization analyses to examine the potential causal associations between gut microbiome and human complex diseases. We found that Saccharibacteria (also known as TM7 phylum) could potentially improve renal function by affecting renal function biomarkers (i.e., creatinine and estimated glomerular filtration rate). In contrast, atrial fibrillation, chronic kidney disease and prostate cancer, as predicted by the host genetics, had potential causal effect on gut microbiome. Further disease-microbiome feature analysis suggested that gut microbiome features revealed novel relationship among human complex diseases. These results suggest that different human complex diseases share common and distinct gut microbiome features, which may help re-shape our understanding about the disease etiology in humans.

scholarly journals The interplay between host genetics and the gut microbiome reveals common and distinct microbiome features for human complex diseases

2020 ◽  
Author(s):  
Fengzhe Xu ◽  
Yuanqing Fu ◽  
Tingyu Sun ◽  
Zengliang Jiang ◽  
Zelei Miao ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Lupus Erythematosus ◽  
Gut Microbiome ◽  
Odds Ratio ◽  
Genome Wide Association Study ◽  
Causal Effect ◽  
Complex Diseases ◽  
Disease Etiology ◽  
Host Genetics ◽  
Human Complex

Abstract Background There is increasing interest about the interplay between host genetics and gut microbiome on human complex diseases, with prior evidence mainly derived from animal models. In addition, the shared and distinct microbiome features among human complex diseases remain largely unclear.Results The analysis was based on a Chinese population with 1,475 participants. We estimated the SNP-based heritability, which suggested that Desulfovibrionaceae and Odoribacter had significant heritability estimates (0.456 and 0.476, respectively). We performed a microbiome genome-wide association study to identify host genetic variants associated with gut microbiome.We then conducted bi-directional Mendelian randomization analyses to examine the potential causal associations between gut microbiome and human complex diseases. We found that Saccharibacteria (per 1-SD higher in the log-transformed abundance) could potentially decrease the concentration of serum creatinine (Beta: -0.011 [95%CI: -0.019, -0.003], p=0.007) and increase estimated glomerular filtration rate (Beta: 0.012 [95%CI: 0.004, 0.020], p=0.003). On the other hand, atrial fibrillation, chronic kidney disease and prostate cancer, as predicted by the host genetics, had potential causal effect on the abundance of some specific gut microbiota. For example, atrial fibrillation (per log odds) could increase the abundance of Burkholderiales (Beta: 0.079[95%CI: 0.009, 0.150], p=0.027) and Alcaligenaceae (Beta: 0.082[95%CI: 0.012, 0.152], p=0.022), and decrease the abundance of Lachnobacterium (Beta:-0.078[95%CI: -0.148, -0.006], p=0.034), Bacteroides coprophilus (Beta: -0.113[95%CI: -0.184, -0.041], p=0.002), Barnesiellaceae (odds ratio: 0.818[95%CI: 0.686, 0.976], p=0.026), Veillonellaceae undefined (odds ratio: 0.801[95%CI: 0.669, 0.960], p=0.017) as well as Mitsuokella (odds ratio: 0.657[95%CI: 0.496, 0.870], p=0.003). Further disease-microbiome feature analysis suggested that systemic lupus erythematosus and chronic myeloid leukemia shared common gut microbiome features.Conclusions These results suggest that different human complex diseases share common and distinct gut microbiome features, which may help re-shape our understanding about the disease etiology in humans.

scholarly journals The interplay between host genetics and the gut microbiome reveals common and distinct microbiome features for complex human diseases

2020 ◽  
Author(s):  
Fengzhe Xu ◽  
Yuanqing Fu ◽  
Tingyu Sun ◽  
Zengliang Jiang ◽  
Zelei Miao ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Lupus Erythematosus ◽  
Gut Microbiome ◽  
Genome Wide Association Study ◽  
Human Diseases ◽  
Host Genetics ◽  
Genome Wide ◽  
Disease Aetiology ◽  
Significant Heritability ◽  
Host Genetic

Abstract Background Interest in the interplay between host genetics and the gut microbiome in complex human diseases is increasing, with prior evidence mainly being derived from animal models. In addition, the shared and distinct microbiome features among complex human diseases remain largely unclear.Results This analysis was based on a Chinese population with 1,475 participants. We estimated the SNP-based heritability, which suggested that Desulfovibrionaceae and Odoribacter had significant heritability estimates (0.456 and 0.476, respectively). We performed a microbiome genome-wide association study to identify host genetic variants associated with the gut microbiome. We then conducted bidirectional Mendelian randomization analyses to examine the potential causal associations between the gut microbiome and complex human diseases. We found that Saccharibacteria could potentially decrease the concentration of serum creatinine and increase the estimated glomerular filtration rate. On the other hand, atrial fibrillation, chronic kidney disease and prostate cancer, as predicted by host genetics, had potential causal effects on the abundance of some specific gut microbiota. For example, atrial fibrillation increased the abundance of Burkholderiales and Alcaligenaceae and decreased the abundance of Lachnobacterium, Bacteroides coprophilus, Barnesiellaceae, undefined genus in family Veillonellaceae and Mitsuokella. Further disease-microbiome feature analysis suggested that systemic lupus erythematosus and chronic myeloid leukaemia shared common gut microbiome features.Conclusions These results suggest that different complex human diseases share common and distinct gut microbiome features, which may help reshape our understanding of disease aetiology in humans.

scholarly journals The interplay between host genetics and the gut microbiome reveals common and distinct microbiome features for complex human diseases

Microbiome ◽  
2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Fengzhe Xu ◽  
Yuanqing Fu ◽  
Ting-yu Sun ◽  
Zengliang Jiang ◽  
Zelei Miao ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Lupus Erythematosus ◽  
Gut Microbiome ◽  
Genome Wide Association Study ◽  
Human Diseases ◽  
Host Genetics ◽  
Genome Wide ◽  
Disease Aetiology ◽  
Significant Heritability ◽  
Host Genetic

Abstract Background Interest in the interplay between host genetics and the gut microbiome in complex human diseases is increasing, with prior evidence mainly being derived from animal models. In addition, the shared and distinct microbiome features among complex human diseases remain largely unclear. Results This analysis was based on a Chinese population with 1475 participants. We estimated the SNP-based heritability, which suggested that Desulfovibrionaceae and Odoribacter had significant heritability estimates (0.456 and 0.476, respectively). We performed a microbiome genome-wide association study to identify host genetic variants associated with the gut microbiome. We then conducted bidirectional Mendelian randomization analyses to examine the potential causal associations between the gut microbiome and complex human diseases. We found that Saccharibacteria could potentially decrease the concentration of serum creatinine and increase the estimated glomerular filtration rate. On the other hand, atrial fibrillation, chronic kidney disease and prostate cancer, as predicted by host genetics, had potential causal effects on the abundance of some specific gut microbiota. For example, atrial fibrillation increased the abundance of Burkholderiales and Alcaligenaceae and decreased the abundance of Lachnobacterium, Bacteroides coprophilus, Barnesiellaceae, an undefined genus in the family Veillonellaceae and Mitsuokella. Further disease-microbiome feature analysis suggested that systemic lupus erythematosus and chronic myeloid leukaemia shared common gut microbiome features. Conclusions These results suggest that different complex human diseases share common and distinct gut microbiome features, which may help reshape our understanding of disease aetiology in humans.

scholarly journals The interplay between host genetics and the gut microbiome reveals common and distinct microbiome features for complex human diseases

2020 ◽  
Author(s):  
Fengzhe Xu ◽  
Yuanqing Fu ◽  
Tingyu Sun ◽  
Zengliang Jiang ◽  
Zelei Miao ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Lupus Erythematosus ◽  
Gut Microbiome ◽  
Genome Wide Association Study ◽  
Human Diseases ◽  
Host Genetics ◽  
Genome Wide ◽  
Disease Aetiology ◽  
Significant Heritability ◽  
Host Genetic

Abstract Background Interest in the interplay between host genetics and the gut microbiome in complex human diseases is increasing, with prior evidence mainly being derived from animal models. In addition, the shared and distinct microbiome features among complex human diseases remain largely unclear.Results This analysis was based on a Chinese population with 1,475 participants. We estimated the SNP-based heritability, which suggested that Desulfovibrionaceae and Odoribacter had significant heritability estimates (0.456 and 0.476, respectively). We performed a microbiome genome-wide association study to identify host genetic variants associated with the gut microbiome. We then conducted bidirectional Mendelian randomization analyses to examine the potential causal associations between the gut microbiome and complex human diseases. We found that Saccharibacteria could potentially decrease the concentration of serum creatinine and increase the estimated glomerular filtration rate. On the other hand, atrial fibrillation, chronic kidney disease and prostate cancer, as predicted by host genetics, had potential causal effects on the abundance of some specific gut microbiota. For example, atrial fibrillation increased the abundance of Burkholderiales and Alcaligenaceae and decreased the abundance of Lachnobacterium, Bacteroides coprophilus, Barnesiellaceae, an undefined genus in the family Veillonellaceae and Mitsuokella. Further disease-microbiome feature analysis suggested that systemic lupus erythematosus and chronic myeloid leukaemia shared common gut microbiome features. Conclusions These results suggest that different complex human diseases share common and distinct gut microbiome features, which may help reshape our understanding of disease aetiology in humans.

scholarly journals Effect of host genetics on the gut microbiome in 7,738 participants of the Dutch Microbiome Project

2020 ◽  
Author(s):  
E.A. Lopera-Maya ◽  
A. Kurilshikov ◽  
A. van der Graaf ◽  
S. Hu ◽  
S. Andreu-Sánchez ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Genome Wide Association Study ◽  
Strongly Correlated ◽  
Microbial Composition ◽  
Host Genetics ◽  
Secretor Status ◽  
Genome Wide ◽  
A Genome ◽  
And Function ◽  
Larger Sample

AbstractHost genetics are known to influence the gut microbiome, yet their role remains poorly understood. To robustly characterize these effects, we performed a genome-wide association study of 207 taxa and 205 pathways representing microbial composition and function within the Dutch Microbiome Project, a population cohort of 7,738 individuals from the northern Netherlands. Two robust, study-wide significant (p<1.89×10−10) signals near the LCT and ABO genes were found to affect multiple microbial taxa and pathways, and were replicated in two independent cohorts. The LCT locus associations were modulated by lactose intake, while those at ABO reflected participant secretor status determined by FUT2 genotype. Eighteen other loci showed suggestive evidence (p<5×10−8) of association with microbial taxa and pathways. At a more lenient threshold, the number of loci identified strongly correlated with trait heritability, suggesting that much larger sample sizes are needed to elucidate the remaining effects of host genetics on the gut microbiome.

scholarly journals Causal effect of renal function on venous thromboembolism: a two-sample Mendelian randomization investigation

2021 ◽  
Author(s):  
Shuai Yuan ◽  
Maria Bruzelius ◽  
Susanna C. Larsson
Keyword(s):  
Renal Function ◽  
Venous Thromboembolism ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Genome Wide ◽  
Increased Risk ◽  
Mr Study

AbstractWhether renal function is causally associated with venous thromboembolism (VTE) is not yet fully elucidated. We conducted a two-sample Mendelian randomization (MR) study to determine the causal effect of renal function, measured as estimated glomerular filtration rate (eGFR), on VTE. Single-nucleotide polymorphisms associated with eGFR were selected as instrumental variables at the genome-wide significance level (p < 5 × 10−8) from a meta-analysis of 122 genome-wide association studies including up to 1,046,070 individuals. Summary-level data for VTE were obtained from the FinnGen consortium (6913 VTE cases and 169,986 non-cases) and UK Biobank study (4620 VTE cases and 356,574 non-cases). MR estimates were calculated using the random-effects inverse-variance weighted method and combined using fixed-effects meta-analysis. Genetically predicted decreased eGFR was significantly associated with an increased risk of VTE in both FinnGen and UK Biobank. For one-unit decrease in log-transformed eGFR, the odds ratios of VTE were 2.93 (95% confidence interval (CI) 1.25, 6.84) and 4.46 (95% CI 1.59, 12.5) when using data from FinnGen and UK Biobank, respectively. The combined odds ratio was 3.47 (95% CI 1.80, 6.68). Results were consistent in all sensitivity analyses and no horizontal pleiotropy was detected. This MR-study supported a casual role of impaired renal function in VTE.

scholarly journals Host Genetic Factors Associated with Vaginal Microbiome Composition in Kenyan Women

mSystems ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
Supriya D. Mehta ◽  
Drew R. Nannini ◽  
Fredrick Otieno ◽  
Stefan J. Green ◽  
Walter Agingu ◽  
...  
Keyword(s):  
Racial Differences ◽  
Genome Wide Association Study ◽  
Vaginal Microbiome ◽  
Content Type ◽  
Microbiome Composition ◽  
Genome Wide ◽  
A Genome ◽  
Kenyan Women ◽  
Host Genetic ◽  
Women Of African Descent

ABSTRACT Bacterial vaginosis (BV) affects 20% of women worldwide and is associated with adverse reproductive health outcomes and increased risk for HIV. Typically, BV represents a shift in the vaginal microbiome from one that is dominated by Lactobacillus to one that is diverse. Persistent racial differences in BV and diverse vaginal microbiome composition overlap with racial disparities in risks for HIV and sexually transmitted infection, especially among women of African descent. Risk factors for BV and nonoptimal vaginal microbiome include sexual practices, yet racial differences persist when adjusted for behavioral factors, suggesting a host genetic component. Here, we perform a genome-wide association study on vaginal microbiome traits in Kenyan women. Linear regression and logistic regression were performed, adjusting for age and principal components of genetic ancestry, to evaluate the association between Lactobacillus crispatus, Lactobacillus iners, Gardnerella vaginalis, Shannon diversity index, and community state type (CST) with host genetic single nucleotide polymorphisms (SNPs). We identified novel genomic loci associated with the vaginal microbiome traits, though no SNP reached genome-wide significance. During pathway enrichment analysis, Toll-like receptors (TLRs), cytokine production, and other components of innate immune response were associated with L. crispatus, L. iners, and CST. Multiple previously reported genomic loci were replicated, including IL-8 (Shannon, CST), TIRAP (L. iners, Shannon), TLR2 (Shannon, CST), MBL2 (L. iners, G. vaginalis, CST), and MYD88 (L. iners, Shannon). These genetic associations suggest a role for the innate immune system and cell signaling in vaginal microbiome composition and susceptibility to nonoptimal vaginal microbiome. IMPORTANCE Globally, bacterial vaginosis (BV) is a common condition in women. BV is associated with poorer reproductive health outcomes and HIV risk. Typically, BV represents a shift in the vaginal microbiome from one that is dominated by Lactobacillus to one that is diverse. Despite many women having similar exposures, the prevalence of BV and nonoptimal vaginal microbiome is increased for women of African descent, suggesting a possible role for host genetics. We conducted a genome-wide association study of important vaginal microbiome traits in Kenyan women. We identified novel genetic loci and biological pathways related to mucosal immunity, cell signaling, and infection that were associated with vaginal microbiome traits; we replicated previously reported loci associated with mucosal immune response. These results provide insight into potential host genetic influences on vaginal microbiome composition and can guide larger longitudinal studies, with genetic and functional comparison across microbiome sites within individuals and across populations.

scholarly journals Genome-Wide Association Study of Human Immunodeficiency Virus (HIV)-1 Coreceptor Usage in Treatment-Naive Patients from An AIDS Clinical Trials Group Study

2014 ◽  
Vol 1 (1) ◽  
Author(s):  
Timothy J. Henrich ◽  
Paul J. McLaren ◽  
Suhas S. P. Rao ◽  
Nina H. Lin ◽  
Emily Hanhauser ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Coreceptor Usage ◽  
Genome Wide ◽  
Immunodeficiency Virus ◽  
Treatment Naïve ◽  
Host Genetic ◽  
Aids Clinical Trials ◽  
Hiv 1

Abstract Objectives.  We conducted a genome-wide association study to explore whether common host genetic variants (&gt;5% frequency) were associated with presence of virus able to use CXCR4 for entry. Methods.  Phenotypic determination of human immunodeficiency virus (HIV)-1 coreceptor usage was performed on pretreatment plasma HIV-1 samples from treatment-naive participants in AIDS Clinical Trials Group A5095, a study of initial antiretroviral regimens. Associations between genome-wide single-nucleotide polymorphisms (SNPs), CCR5 Δ32 genotype, and human leukocyte antigen (HLA) class I alleles and viral coreceptor usage were explored. Results.  Viral phenotypes were obtained from 593 patients with available genome-wide SNP data. Forty-four percent of subjects had virus capable of using CXCR4 for entry as determined by phenotyping. Overall, no associations, including those between polymorphisms in genes encoding viral coreceptors and their promoter regions or in HLA genes previously associated with HIV-1 disease progression, passed the statistical threshold for genome-wide significance (P &lt; 5.0 × 10−8) in any comparison. However, the presence of viruses able to use CXCR4 for entry was marginally associated with the CCR5 Δ32 genotype in the nongenome-wide analysis. Conclusions.  No human genetic variants were significantly associated with virus able to use CXCR4 for entry at the genome-wide level. Although the sample size had limited power to definitively exclude genetic associations, these results suggest that host genetic factors, including those that influence coreceptor expression or the immune pressures leading to viral envelope diversity, are either rare or have only modest effects in determining HIV-1 coreceptor usage.

scholarly journals Assessing causality in associations between cannabis use and schizophrenia risk: a two-sample Mendelian randomization study

2016 ◽  
Vol 47 (5) ◽  
pp. 971-980 ◽  
Author(s):  
S. H. Gage ◽  
H. J. Jones ◽  
S. Burgess ◽  
J. Bowden ◽  
G. Davey Smith ◽  
...  
Keyword(s):  
Fixed Effects ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Positive Control ◽  
Negative Control ◽  
Study Data ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
Genome Wide Data

BackgroundObservational associations between cannabis and schizophrenia are well documented, but ascertaining causation is more challenging. We used Mendelian randomization (MR), utilizing publicly available data as a method for ascertaining causation from observational data.MethodWe performed bi-directional two-sample MR using summary-level genome-wide data from the International Cannabis Consortium (ICC) and the Psychiatric Genomics Consortium (PGC2). Single nucleotide polymorphisms (SNPs) associated with cannabis initiation (p < 10−5) and schizophrenia (p < 5 × 10−8) were combined using an inverse-variance-weighted fixed-effects approach. We also used height and education genome-wide association study data, representing negative and positive control analyses.ResultsThere was some evidence consistent with a causal effect of cannabis initiation on risk of schizophrenia [odds ratio (OR) 1.04 per doubling odds of cannabis initiation, 95% confidence interval (CI) 1.01–1.07, p = 0.019]. There was strong evidence consistent with a causal effect of schizophrenia risk on likelihood of cannabis initiation (OR 1.10 per doubling of the odds of schizophrenia, 95% CI 1.05–1.14, p = 2.64 × 10−5). Findings were as predicted for the negative control (height: OR 1.00, 95% CI 0.99–1.01, p = 0.90) but weaker than predicted for the positive control (years in education: OR 0.99, 95% CI 0.97–1.00, p = 0.066) analyses.ConclusionsOur results provide some that cannabis initiation increases the risk of schizophrenia, although the size of the causal estimate is small. We find stronger evidence that schizophrenia risk predicts cannabis initiation, possibly as genetic instruments for schizophrenia are stronger than for cannabis initiation.

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